Recently developed sensitive silver strains allow detection of trace proteins. Computerized microdensitometry has added a third dimension, quantitation to the two-dimensional electrophoretograms. These techniques were used to examine the Lesch-Nyhan syndrome. Four hundred lymphocyte proteins were analyzed on each electrophoretogram. Quantitative differences were found in the lymphocyte autoradiograms. Eleven which were significantly different at the 2P less than .01 level. This study indicates that characteristic secondary changes in proteins may be observed, permitting the establishment of a catalogue of protein changes in metabolic diseases. This technology has also been used to study proteins affected by chromosome 21, the chromosome associated with Down's syndrome. A quantitative correlation has been found in gel analysis between the protein superoxide dismulate, coded for by chromosome 21, and the number of chromosome copies pr cell. Location of the galactose operon gene products from E. coli in 2-D electrophoretograms are allowing us to monitor human cells containing E. coli genes in various vectors.